Dudli Stefan, Sing David C, Hu Serena S, Berven Sigurd H, Burch Shane, Deviren Vedat, Cheng Ivan, Tay Bobby K B, Alamin Todd F, Ith Ma Agnes Martinez, Pietras Eric M, Lotz Jeffrey C
Department of Orthopaedic Surgery, University of California San Francisco, 513 Parnassus Ave, S-1164, San Francisco, CA, 94143, USA.
Stanford Spine Clinic, Stanford University Medical Center, Stanford, USA.
Eur Spine J. 2017 May;26(5):1362-1373. doi: 10.1007/s00586-017-4955-4. Epub 2017 Jan 31.
Cross-sectional cohort analysis of patients with Modic Changes (MC).
Our goal was to characterize the molecular and cellular features of MC bone marrow and adjacent discs. We hypothesized that MC associate with biologic cross-talk between discs and bone marrow, the presence of which may have both diagnostic and therapeutic implications.
MC are vertebral bone marrow lesions that can be a diagnostic indicator for discogenic low back pain. Yet, the pathobiology of MC is largely unknown.
Patients with Modic type 1 or 2 changes (MC1, MC2) undergoing at least 2-level lumbar interbody fusion with one surgical level having MC and one without MC (control level). Two discs (MC, control) and two bone marrow aspirates (MC, control) were collected per patient. Marrow cellularity was analyzed using flow cytometry. Myelopoietic differentiation potential of bone marrow cells was quantified to gauge marrow function, as was the relative gene expression profiles of the marrow and disc cells. Disc/bone marrow cross-talk was assessed by comparing MC disc/bone marrow features relative to unaffected levels.
Thirteen MC1 and eleven MC2 patients were included. We observed pro-osteoclastic changes in MC2 discs, an inflammatory dysmyelopoiesis with fibrogenic changes in MC1 and MC2 marrow, and up-regulation of neurotrophic receptors in MC1 and MC2 bone marrow and discs.
Our data reveal a fibrogenic and pro-inflammatory cross-talk between MC bone marrow and adjacent discs. This provides insight into the pain generator at MC levels and informs novel therapeutic targets for treatment of MC-associated LBP.
对患有Modic改变（MC）的患者进行横断面队列分析。
我们的目标是描述MC骨髓和相邻椎间盘的分子及细胞特征。我们假设MC与椎间盘和骨髓之间的生物学相互作用有关，其存在可能具有诊断和治疗意义。
MC是椎体骨髓病变，可作为椎间盘源性下腰痛的诊断指标。然而，MC的病理生物学在很大程度上尚不清楚。
患有Modic 1型或2型改变（MC1、MC2）的患者接受至少两级腰椎椎间融合术，其中一个手术节段有MC，另一个无MC（对照节段）。每位患者收集两个椎间盘（MC、对照）和两份骨髓抽吸物（MC、对照）。使用流式细胞术分析骨髓细胞密度。对骨髓细胞的髓系分化潜能进行量化以评估骨髓功能，同时也对骨髓和椎间盘细胞的相对基因表达谱进行了分析。通过比较MC椎间盘/骨髓特征与未受影响节段来评估椎间盘/骨髓的相互作用。
纳入了13例MC1患者和11例MC2患者。我们观察到MC2椎间盘有促破骨细胞变化，MC1和MC2骨髓有炎症性骨髓生成异常伴纤维化改变，以及MC1和MC2骨髓及椎间盘中神经营养受体上调。
我们的数据揭示了MC骨髓与相邻椎间盘之间的纤维化和促炎相互作用。这为MC节段的疼痛产生机制提供了见解，并为治疗与MC相关的下腰痛提供了新的治疗靶点。
